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Downregulation of renal sodium transporters in obstructed kidneys could contribute to impaired urinary concentrating capability and salt waste following the release of a ureteral obstruction. The current study was undertaken to investigate the role of mitochondrial complex-1 inhibition in modulating sodium transporters in obstructive kidney disease. Following unilateral ureteral obstruction (UUO) for 7 days, a global reduction of sodium transporters, including NHE3, \u03b1-Na-K-ATPase, NCC, NKCC2, p-NKCC2, ENaC\u03b1 and ENaC\u03b3, was observed, as determined via qRT-PCR and\/or Western blotting. Interestingly, inhibition of mitochondrial complex-1 by rotenone markedly reversed the downregulation of NKCC2, p-NKCC2 and ENaC\u03b1. In contrast, other sodium transporters were not affected by rotenone. To study the potential mechanisms involved in mediating the effects of rotenone on sodium transporters, we examined a number of known sodium modulators, including PGE2, ET1, Ang II, natriuretic peptides (ANP, BNP and CNP) and nitric oxide synthases (iNOS, nNOS and eNOS). Importantly, among these modulators, only BNP and iNOS were significantly reduced by rotenone treatment. Collectively, these findings demonstrated a substantial role of mitochondrial dysfunction in mediating the downregulation of NKCC2 and ENaC\u03b1 in obstructive kidney disease, possibly via iNOS-derived nitric oxide and BNP.<\/jats:p>","DOI":"10.1038\/srep12480","type":"journal-article","created":{"date-parts":[[2015,7,24]],"date-time":"2015-07-24T12:46:35Z","timestamp":1437741995000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibition of Mitochondrial Complex-1 Prevents the Downregulation of NKCC2 and ENaC\u03b1 in Obstructive Kidney Disease"],"prefix":"10.1038","volume":"5","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guixia","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songming","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aihua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanjun","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,7,24]]},"reference":[{"key":"BFsrep12480_CR1","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1111\/iju.12606","volume":"22","author":"F Ahmadi","year":"2015","unstructured":"Ahmadi, F. et al. 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